Title |
Outer Membrane Vesicles Prime and Activate Macrophage Inflammasomes and Cytokine Secretion In Vitro and In Vivo
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Published in |
Frontiers in immunology, August 2017
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DOI | 10.3389/fimmu.2017.01017 |
Pubmed ID | |
Authors |
Jessica D. Cecil, Neil M. O’Brien-Simpson, Jason C. Lenzo, James A. Holden, William Singleton, Alexis Perez-Gonzalez, Ashley Mansell, Eric C. Reynolds |
Abstract |
Outer membrane vesicles (OMVs) are proteoliposomes blebbed from the surface of Gram-negative bacteria. Chronic periodontitis is associated with an increase in subgingival plaque of Gram-negative bacteria, Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. In this study, we investigated the immune-modulatory effects of P. gingivalis, T. denticola, and T. forsythia OMVs on monocytes and differentiated macrophages. All of the bacterial OMVs were phagocytosed by monocytes, M(naïve) and M(IFNγ) macrophages in a dose-dependent manner. They also induced NF-κB activation and increased TNFα, IL-8, and IL-1β cytokine secretion. P. gingivalis OMVs were also found to induce anti-inflammatory IL-10 secretion. Although unprimed monocytes and macrophages were resistant to OMV-induced cell death, lipopolysaccharide or OMV priming resulted in a significantly reduced cell viability. P. gingivalis, T. denticola, and T. forsythia OMVs all activated inflammasome complexes, as monitored by IL-1β secretion and ASC speck formation. ASC was critical for OMV-induced inflammasome formation, while AIM2-/- and Caspase-1-/- cells had significantly reduced inflammasome formation and NLRP3-/- cells exhibited a slight reduction. OMVs were also found to provide both priming and activation of the inflammasome complex. High-resolution microscopy and flow cytometry showed that P. gingivalis OMVs primed and activated macrophage inflammasomes in vivo with 80% of macrophages exhibiting inflammasome complex formation. In conclusion, periodontal pathogen OMVs were found to have significant immunomodulatory effects upon monocytes and macrophages and should therefore influence pro-inflammatory host responses associated with disease. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 133 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 29 | 22% |
Student > Master | 19 | 14% |
Student > Bachelor | 14 | 11% |
Researcher | 11 | 8% |
Student > Doctoral Student | 7 | 5% |
Other | 17 | 13% |
Unknown | 36 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Immunology and Microbiology | 31 | 23% |
Agricultural and Biological Sciences | 24 | 18% |
Biochemistry, Genetics and Molecular Biology | 21 | 16% |
Pharmacology, Toxicology and Pharmaceutical Science | 5 | 4% |
Medicine and Dentistry | 5 | 4% |
Other | 4 | 3% |
Unknown | 43 | 32% |